Biochemistry and Molecular Biology - Belyasova N.A. 2002

Metabolism. Energy-Yielding Processes
Tricarboxylic Acid Cycle
Regulation of the TCA Cycle

The rate of TCA cycle functioning is regulated at multiple levels and is precisely tuned to the metabolic needs of The Cell. The primary rate-limiting reaction of the cycle is The oxidative decarboxylation of isocitrate. Isocitrate dehydrogenase is an allosteric protein activated by adenosine diphosphate, which increases the enzyme's affinity for its substrates. The activity of isocitrate dehydrogenase is inhibited by NADH, which displaces NAD⁺ from the Active Site.

Another TCA cycle enzyme, citrate synthase, is subject to inhibition by ATP: as the intracellular ATP concentration rises, the saturation of the enzyme's active site with acetyl-CoA decreases, leading to a reduction in the rate of citrate formation.

Yet another TCA cycle enzyme, succinate dehydrogenase, modulates its activity through Allosteric Regulation: it is activated by phosphate and succinate, and inhibited by oxaloacetate. The accumulation of OAA within the cell prevents The oxidation of succinate.

Finally, the activity of a-ketoglutarate dehydrogenase is allosterically inhibited by the products of the reaction it catalyzes—succinyl-CoA and NADH.

It should be noted that various organisms may employ different mechanisms for regulating TCA cycle kinetics, including those not described here.